Effects of 5-FU and anti-EGFR antibody in combination with ASA on the spherical culture system of HCT116 and HT29 colorectal cancer cell lines

  • Authors:
    • Agata Olejniczak-Kęder
    • Magdalena Szaryńska
    • Agata Wrońska
    • Kamila Siedlecka-Kroplewska
    • Zbigniew Kmieć
  • View Affiliations

  • Published online on: May 23, 2019     https://doi.org/10.3892/ijo.2019.4809
  • Pages: 223-242
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Abstract

The aim of this study was to examine the effects of 5‑fluorouracil (5‑FU), anti‑epidermal growth factor receptor (EGFR) antibody and aspirin (ASA) on the characteristics of two CRC cell lines, HCT116 and HT29, maintained in a spherical culture system. We observed that the morphology of both the HCT116 and HT29 cell‑derived spheres was significantly impaired and the size of the colonospheres was markedly reduced following treatment with the aforementioned three drugs. In contrast to adherent cultures, the spherical cultures were more resistant to the tested drugs, as was reflected by their capacity to re‑create the colonospheres when sustained in serum‑free medium. Flow cytometric analysis of the drug‑treated HCT116 cell‑derived spheres revealed changes in the fraction of cells expressing markers of cancer stem cells (CSCs), whereas the CSC phenotype of HT29 cell‑derived colonospheres was affected to a lesser extent. All reagents enhanced the percentage of non‑viable cells in the colonospheres despite the diminished fraction of active caspase‑3‑positive cells following treatment of the HT29 cell‑derived spheres with anti‑EGFR antibody. Increased autophagy, assessed by acridine orange staining, was noted following the incubation of the HT29‑colonospheres with ASA and 5‑FU in comparison to the control. Notably, the percentage of cyclooxygenase (COX)‑2‑positive cells was not affected by ASA, although its activity was markedly elevated in the colonospheres incubated with anti‑EGFR antibody. On the whole, the findings of this study indicate that all the tested drugs were involved in different cellular processes, which suggests that they should be considered for the combined therapeutic treatment of CRC, particularly for targeting the population of CSC‑like cells. Thus, cancer cell‑derived spheres may be used as a preferable model for in vitro anticancer drug testing.

References

1 

Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global patterns and trends in colorectal cancer incidence and mortality. Gut. 66:683–691. 2017. View Article : Google Scholar

2 

Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C and De Maria R: Identification and expansion of human colon-cancer-initiating cells. Nature. 445:111–115. 2007. View Article : Google Scholar

3 

O'Brien CA, Pollett A, Gallinger S and Dick JE: A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 445:106–110. 2007. View Article : Google Scholar

4 

Chen X, Liao R, Li D and Sun J: Induced cancer stem cells generated by radiochemotherapy and their therapeutic implications. Oncotarget. 8:17301–17312. 2017.

5 

Wang SS, Jiang J, Liang XH and Tang YL: Links between cancer stem cells and epithelial-mesenchymal transition. Onco Targets Ther. 8:2973–2980. 2015.PubMed/NCBI

6 

Celià-Terrassa T and Kang Y: Distinctive properties of metastasis-initiating cells. Genes Dev. 30:892–908. 2016. View Article : Google Scholar : PubMed/NCBI

7 

Hutchinson L and Kirk R: High drug attrition rates--where are we going wrong? Nat Rev Clin Oncol. 8:189–190. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Sant S and Johnston PA: The production of 3D tumor spheroids for cancer drug discovery. Drug Discov Today Technol. 23:27–36. 2017. View Article : Google Scholar : PubMed/NCBI

9 

Karlsson H, Fryknäs M, Larsson R and Nygren P: Loss of cancer drug activity in colon cancer HCT-116 cells during spheroid formation in a new 3-D spheroid cell culture system. Exp Cell Res. 318:1577–1585. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Olejniczak A, Szaryńska M and Kmieć Z: In vitro characterization of spheres derived from colorectal cancer cell lines. Int J Oncol. 52:599–612. 2018.

11 

Costa EC, Moreira AF, de Melo-Diogo D, Gaspar VM, Carvalho MP and Correia IJ: 3D tumor spheroids: An overview on the tools and techniques used for their analysis. Biotechnol Adv. 34:1427–1441. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Qureshi-Baig K, Ullmann P, Rodriguez F, Frasquilho S, Nazarov PV, Haan S and Letellier E: What do we learn from spheroid culture systems? Insights from tumorspheres derived from primary colon cancer tissue. PLoS One. 11:e01460522016. View Article : Google Scholar : PubMed/NCBI

13 

Kim SY, Hong SH, Basse PH, Wu C, Bartlett DL, Kwon YT and Lee YJ: Cancer stem cells protect non-stem cells from anoikis: Bystander effects. J Cell Biochem. 117:2289–2301. 2016. View Article : Google Scholar : PubMed/NCBI

14 

Paoli P, Giannoni E and Chiarugi P: Anoikis molecular pathways and its role in cancer progression. Biochim Biophys Acta. 1833:3481–3498. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Islam F, Gopalan V, Smith RA and Lam AK: Translational potential of cancer stem cells: A review of the detection of cancer stem cells and their roles in cancer recurrence and cancer treatment. Exp Cell Res. 335:135–147. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Siddique HR and Saleem M: Role of BMI1, a stem cell factor, in cancer recurrence and chemoresistance: Preclinical and clinical evidences. Stem Cells. 30:372–378. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Yan KS, Chia LA, Li X, Ootani A, Su J, Lee JY, Su N, Luo Y, Heilshorn SC, Amieva MR, et al: The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations. Proc Natl Acad Sci USA. 109:466–471. 2012. View Article : Google Scholar

18 

Manhas J, Bhattacharya A, Agrawal SK, Gupta B, Das P, Deo SV, Pal S and Sen S: Characterization of cancer stem cells from different grades of human colorectal cancer. Tumour Biol. 37:14069–14081. 2016. View Article : Google Scholar : PubMed/NCBI

19 

Butler SJ, Richardson L, Farias N, Morrison J and Coomber BL: Characterization of cancer stem cell drug resistance in the human colorectal cancer cell lines HCT116 and SW480. Biochem Biophys Res Commun. 490:29–35. 2017. View Article : Google Scholar : PubMed/NCBI

20 

Szaryńska M, Olejniczak A, Kobiela J, Spychalski P and Kmieć Z: Therapeutic strategies against cancer stem cells in human colorectal cancer. Oncol Lett. 14:7653–7668. 2017.

21 

Chan AT, Manson JE, Feskanich D, Stampfer MJ, Colditz GA and Fuchs CS: Long-term aspirin use and mortality in women. Arch Intern Med. 167:562–572. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Thorat MA and Cuzick J: Role of aspirin in cancer prevention. Curr Oncol Rep. 15:533–540. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Din FV, Valanciute A, Houde VP, Zibrova D, Green KA, Sakamoto K, Alessi DR and Dunlop MG: Aspirin inhibits mTOR signaling, activates AMP-activated protein kinase, and induces autophagy in colorectal cancer cells. Gastroenterology. 142:1504–1515.e1503. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Kaur J and Sanyal SN: PI3-kinase/Wnt association mediates COX-2/PGE(2) pathway to inhibit apoptosis in early stages of colon carcinogenesis: Chemoprevention by diclofenac. Tumour Biol. 31:623–631. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Saha S, Mukherjee S, Khan P, Kajal K, Mazumdar M, Manna A, Mukherjee S, De S, Jana D, Sarkar DK, et al: Aspirin suppresses the acquisition of chemoresistance in breast cancer by disrupting an NFkappaB-IL6 signaling axis responsible for the generation of cancer stem cells. Cancer Res. 76:2000–2012. 2016. View Article : Google Scholar : PubMed/NCBI

26 

Kastrati I, Litosh VA, Zhao S, Alvarez M, Thatcher GR and Frasor J: A novel aspirin prodrug inhibits NFκB activity and breast cancer stem cell properties. BMC Cancer. 15:8452015. View Article : Google Scholar

27 

Moon CM, Kwon JH, Kim JS, Oh SH, Jin Lee K, Park JJ, Pil Hong S, Cheon JH, Kim TI and Kim WH: Nonsteroidal anti-inflammatory drugs suppress cancer stem cells via inhibiting PTGS2 (cyclooxygenase 2) and NOTCH/HES1 and activating PPARG in colorectal cancer. Int J Cancer. 134:519–529. 2014. View Article : Google Scholar

28 

Miyamoto Y, Suyama K and Baba H: Recent advances in targeting the EGFR signaling pathway for the treatment of metastatic colorectal cancer. Int J Mol Sci. 18:182017. View Article : Google Scholar

29 

Van Emburgh BO, Sartore-Bianchi A, Di Nicolantonio F, Siena S and Bardelli A: Acquired resistance to EGFR-targeted therapies in colorectal cancer. Mol Oncol. 8:1084–1094. 2014. View Article : Google Scholar : PubMed/NCBI

30 

Goel A, Chang DK, Ricciardiello L, Gasche C and Boland CR: A novel mechanism for aspirin-mediated growth inhibition of human colon cancer cells. Clin Cancer Res. 9:383–390. 2003.PubMed/NCBI

31 

Wang H, Liu B, Wang J, Li J, Gong Y, Li S, Wang C, Cui B, Xue X, Yang M, et al: Reduction of NANOG mediates the inhibitory effect of aspirin on tumor growth and stemness in colorectal cancer. Cell Physiol Biochem. 44:1051–1063. 2017. View Article : Google Scholar : PubMed/NCBI

32 

Mhaidat N M and Bouk lihacene M: 5-Fluorouracil-induced apoptosis in colorectal cancer cells is caspase-9-dependent and mediated by activation of protein kinase C-δ. Oncol Lett. 8:699–704. 2014. View Article : Google Scholar : PubMed/NCBI

33 

Virgone-Carlotta A, Lemasson M, Mertani HC, Diaz JJ, Monnier S, Dehoux T, Delanoë-Ayari H, Rivière C and Rieu JP: In-depth phenotypic characterization of multicellular tumor spheroids: Effects of 5-Fluorouracil. PLoS One. 12:e01881002017. View Article : Google Scholar : PubMed/NCBI

34 

Martin-Villalba A, Llorens-Bobadilla E and Wollny D: CD95 in cancer: Tool or target? Trends Mol Med. 19:329–335. 2013. View Article : Google Scholar : PubMed/NCBI

35 

Chen L, Park SM, Tumanov AV, Hau A, Sawada K, Feig C, Turner JR, Fu YX, Romero IL, Lengyel E, et al: CD95 promotes tumour growth. Nature. 465:492–496. 2010. View Article : Google Scholar : PubMed/NCBI

36 

Szarynska M, Olejniczak A, Wierzbicki P, Kobiela J, Laski D, Sledzinski Z, Adrych K, Guzek M and Kmiec Z: FasR and FasL in colorectal cancer. Int J Oncol. 51:975–986. 2017. View Article : Google Scholar : PubMed/NCBI

37 

Ceppi P, Hadji A, Kohlhapp FJ, Pattanayak A, Hau A, Liu X, Liu H, Murmann AE and Peter ME: CD95 and CD95L promote and protect cancer stem cells. Nat Commun. 5:52382014. View Article : Google Scholar : PubMed/NCBI

38 

Mancias JD and Kimmelman AC: Mechanisms of selective autophagy in normal physiology and cancer. J Mol Biol. 428:1659–1680. 2016. View Article : Google Scholar : PubMed/NCBI

39 

Vaiopoulos AG, Kostakis ID, Koutsilieris M and Papavassiliou AG: Colorectal cancer stem cells. Stem Cells. 30:363–371. 2012. View Article : Google Scholar : PubMed/NCBI

40 

Gao XL, Zhang M, Tang YL and Liang XH: Cancer cell dormancy: Mechanisms and implications of cancer recurrence and metastasis. OncoTargets Ther. 10:5219–5228. 2017. View Article : Google Scholar

41 

Takeishi S and Nakayama KI: To wake up cancer stem cells, or to let them sleep, that is the question. Cancer Sci. 107:875–881. 2016. View Article : Google Scholar : PubMed/NCBI

42 

Kreso A and Dick JE: Evolution of the cancer stem cell model. Cell Stem Cell. 14:275–291. 2014. View Article : Google Scholar : PubMed/NCBI

43 

Weiswald LB, Bellet D and Dangles-Marie V: Spherical cancer models in tumor biology. Neoplasia. 17:1–15. 2015. View Article : Google Scholar : PubMed/NCBI

44 

Szaryńska M, Olejniczak A, Kobiela J, Łaski D, Śledziński Z and Kmieć Z: Cancer stem cells as targets for DC-based immunotherapy of colorectal cancer. Sci Rep. 8:120422018. View Article : Google Scholar

45 

Drew DA, Cao Y and Chan AT: Aspirin and colorectal cancer: The promise of precision chemoprevention. Nat Rev Cancer. 16:173–186. 2016. View Article : Google Scholar : PubMed/NCBI

46 

Valverde A, Peñarando J, Cañas A, López-Sánchez LM, Conde F, Guil-Luna S, Hernández V, Villar C, Morales-Estévez C, de la Haba-Rodríguez J, et al: The addition of celecoxib improves the antitumor effect of cetuximab in colorectal cancer: Role of EGFR-RAS-FOXM1-β- catenin signaling axis. Oncotarget. 8:21754–21769. 2017. View Article : Google Scholar : PubMed/NCBI

47 

Ahmed D, Eide PW, Eilertsen IA, Danielsen SA, Eknæs M, Hektoen M, Lind GE and Lothe RA: Epigenetic and genetic features of 24 colon cancer cell lines. Oncogenesis. 2:e712013. View Article : Google Scholar : PubMed/NCBI

48 

Kleber S, Sancho-Martinez I, Wiestler B, Beisel A, Gieffers C, Hill O, Thiemann M, Mueller W, Sykora J, Kuhn A, et al: Yes and PI3K bind CD95 to signal invasion of glioblastoma. Cancer Cell. 13:235–248. 2008. View Article : Google Scholar : PubMed/NCBI

49 

Peter ME, Hadji A, Murmann AE, Brockway S, Putzbach W, Pattanayak A and Ceppi P: The role of CD95 and CD95 ligand in cancer. Cell Death Differ. 22:885–886. 2015. View Article : Google Scholar : PubMed/NCBI

50 

De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, Kalogeras KT, Kotoula V, Papamichael D, Laurent-Puig P, et al: Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: A retrospective consortium analysis. Lancet Oncol. 11:753–762. 2010. View Article : Google Scholar : PubMed/NCBI

51 

Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, et al: K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 359:1757–1765. 2008. View Article : Google Scholar : PubMed/NCBI

52 

Gajate P, Sastre J, Bando I, Alonso T, Cillero L, Sanz J, Caldés T and Díaz-Rubio E: Influence of KRAS p.G13D mutation in patients with metastatic colorectal cancer treated with cetuximab. Clin Colorectal Cancer. 11:291–296. 2012. View Article : Google Scholar : PubMed/NCBI

53 

Misale S, Di Nicolantonio F, Sartore-Bianchi A, Siena S and Bardelli A: Resistance to anti-EGFR therapy in colorectal cancer: From heterogeneity to convergent evolution. Cancer Discov. 4:1269–1280. 2014. View Article : Google Scholar : PubMed/NCBI

54 

Allegra CJ, Jessup JM, Somerfield MR, Hamilton SR, Hammond EH, Hayes DF, McAllister PK, Morton RF and Schilsky RL: American Society of Clinical Oncology provisional clinical opinion: Testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol. 27:2091–2096. 2009. View Article : Google Scholar : PubMed/NCBI

55 

De Roock W, Jonker DJ, Di Nicolantonio F, Sartore-Bianchi A, Tu D, Siena S, Lamba S, Arena S, Frattini M, Piessevaux H, et al: Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab. JAMA. 304:1812–1820. 2010. View Article : Google Scholar : PubMed/NCBI

56 

Tejpar S, Celik I, Schlichting M, Sartorius U, Bokemeyer C and Van Cutsem E: Association of KRAS G13D tumor mutations with outcome in patients with metastatic colorectal cancer treated with first-line chemotherapy with or without cetuximab. J Clin Oncol. 30:3570–3577. 2012. View Article : Google Scholar : PubMed/NCBI

57 

Tveit KM, Guren T, Glimelius B, Pfeiffer P, Sorbye H, Pyrhonen S, Sigurdsson F, Kure E, Ikdahl T, Skovlund E, et al: Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: The NORDIC-VII study. J Clin Oncol. 30:1755–1762. 2012. View Article : Google Scholar : PubMed/NCBI

58 

Guren TK, Thomsen M, Kure EH, Sorbye H, Glimelius B, Pfeiffer P, Österlund P, Sigurdsson F, Lothe IM, Dalsgaard AM, et al: Cetuximab in treatment of metastatic colorectal cancer: Final survival analyses and extended RAS data from the NORDIC-VII study. Br J Cancer. 116:1271–1278. 2017. View Article : Google Scholar : PubMed/NCBI

59 

Maughan TS, Adams RA, Smith CG, Meade AM, Seymour MT, Wilson RH, Idziaszczyk S, Harris R, Fisher D, Kenny SL, et al: MRC COIN Trial Investigators: Addition of cetuximab to oxali-platin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: Results of the randomised phase 3 MRC COIN trial. Lancet. 377:2103–2114. 2011. View Article : Google Scholar : PubMed/NCBI

60 

Roelofs HM, Te Morsche RH, van Heumen BW, Nagengast FM and Peters WH: Overexpression of COX-2 mRNA in colorectal cancer. BMC Gastroenterol. 14:12014. View Article : Google Scholar

61 

Lin PC, Lin YJ, Lee CT, Liu HS and Lee JC: Cyclooxygenase-2 expression in the tumor environment is associated with poor prognosis in colorectal cancer patients. Oncol Lett. 6:733–739. 2013. View Article : Google Scholar : PubMed/NCBI

62 

Xu F, Li M, Zhang C, Cui J, Liu J, Li J and Jiang H: Clinicopathological and prognostic significance of COX-2 immu-nohistochemical expression in breast cancer: A meta-analysis. Oncotarget. 8:6003–6012. 2017.

63 

Wang ZM, Liu J, Liu HB, Ye M, Zhang YF and Yang DS: Abnormal COX2 protein expression may be correlated with poor prognosis in oral cancer: A meta-analysis. BioMed Res Int. 2014:3642072014.PubMed/NCBI

64 

Elder DJ, Halton DE, Crew TE and Paraskeva C: Apoptosis induction and cyclooxygenase-2 regulation in human colorectal adenoma and carcinoma cell lines by the cyclooxygenase-2-selective non-steroidal anti-inflammatory drug NS-398. Int J Cancer. 86:553–560. 2000. View Article : Google Scholar : PubMed/NCBI

65 

Xu XT, Hu WT, Zhou JY and Tu Y: Celecoxib enhances the radiosensitivity of HCT116 cells in a COX-2 independent manner by up-regulating BCCIP. Am J Transl Res. 9:1088–1100. 2017.PubMed/NCBI

66 

Alfonso L, Ai G, Spitale RC and Bhat GJ: Molecular targets of aspirin and cancer prevention. Br J Cancer. 111:61–67. 2014. View Article : Google Scholar : PubMed/NCBI

67 

Cao S, Yan Y, Zhang X, Zhang K, Liu C, Zhao G, Han J, Dong Q, Shen B, Wu A, et al: EGF stimulates cyclooxygenase-2 expression through the STAT5 signaling pathway in human lung adenocarcinoma A549 cells. Int J Oncol. 39:383–391. 2011.PubMed/NCBI

68 

Lippman SM, Gibson N, Subbaramaiah K and Dannenberg AJ: Combined targeting of the epidermal growth factor receptor and cyclooxygenase-2 pathways. Clin Cancer Res. 11:6097–6099. 2005. View Article : Google Scholar : PubMed/NCBI

69 

Choe MS, Zhang X, Shin HJ, Shin DM and Chen ZG: Interaction between epidermal growth factor receptor- and cyclooxygenase 2-mediated pathways and its implications for the chemoprevention of head and neck cancer. Mol Cancer Ther. 4:1448–1455. 2005. View Article : Google Scholar : PubMed/NCBI

70 

Huang CY and Yu LC: Pathophysiological mechanisms of death resistance in colorectal carcinoma. World J Gastroenterol. 21:11777–11792. 2015. View Article : Google Scholar : PubMed/NCBI

71 

Kim YM, Park SY and Pyo H: Cyclooxygenase-2 (COX-2) negatively regulates expression of epidermal growth factor receptor and causes resistance to gefitinib in COX-2-overexpressing cancer cells. Mol Cancer Res. 7:1367–1377. 2009. View Article : Google Scholar : PubMed/NCBI

72 

Hu H, Han T, Zhuo M, Wu LL, Yuan C, Wu L, Lei W, Jiao F and Wang LW: Elevated COX-2 expression promotes angio-genesis through EGFR/p38-MAPK/Sp1-dependent signalling in pancreatic cancer. Sci Rep. 7:4702017. View Article : Google Scholar

73 

Shalini S, Dorstyn L, Dawar S and Kumar S: Old, new and emerging functions of caspases. Cell Death Differ. 22:526–539. 2015. View Article : Google Scholar :

74 

Fujita J, Crane AM, Souza MK, Dejosez M, Kyba M, Flavell RA, Thomson JA and Zwaka TP: Caspase activity mediates the differentiation of embryonic stem cells. Cell Stem Cell. 2:595–601. 2008. View Article : Google Scholar : PubMed/NCBI

75 

Janzen V, Fleming HE, Riedt T, Karlsson G, Riese MJ, Lo Celso C, Reynolds G, Milne CD, Paige CJ, Karlsson S, et al: Hematopoietic stem cell responsiveness to exogenous signals is limited by caspase-3. Cell Stem Cell. 2:584–594. 2008. View Article : Google Scholar : PubMed/NCBI

76 

Flanagan L, Meyer M, Fay J, Curry S, Bacon O, Duessmann H, John K, Boland KC, McNamara DA, Kay EW, et al: Low levels of Caspase- 3 predict favourable response to 5FU-based chemotherapy in advanced colorectal cancer: Caspase-3 inhibition as a therapeutic approach. Cell Death Dis. 7:e20872016. View Article : Google Scholar

77 

Liang Y, Yan C and Schor NF: Apoptosis in the absence of caspase 3. Oncogene. 20:6570–6578. 2001. View Article : Google Scholar : PubMed/NCBI

78 

Huang Q, Li F, Liu X, Li W, Shi W, Liu FF, O'Sullivan B, He Z, Peng Y, Tan AC, et al: Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy. Nat Med. 17:860–866. 2011. View Article : Google Scholar : PubMed/NCBI

79 

Li F, Huang Q, Chen J, Peng Y, Roop DR, Bedford JS and Li CY: Apoptotic cells activate the 'phoenix rising' pathway to promote wound healing and tissue regeneration. Sci Signal. 3:ra132010. View Article : Google Scholar

80 

Pietilä M, Lehtonen S, Närhi M, Hassinen IE, Leskelä HV, Aranko K, Nordström K, Vepsäläinen A and Lehenkari P: Mitochondrial function determines the viability and osteogenic potency of human mesenchymal stem cells. Tissue Eng Part C Methods. 16:435–445. 2010. View Article : Google Scholar

81 

Heerdt BG, Houston MA, Wilson AJ and Augenlicht LH: The intrinsic mitochondrial membrane potential (Deltapsim) is associated with steady-state mitochondrial activity and the extent to which colonic epithelial cells undergo butyrate-mediated growth arrest and apoptosis. Cancer Res. 63:6311–6319. 2003.PubMed/NCBI

82 

Heerdt BG, Houston MA and Augenlicht LH: The intrinsic mitochondrial membrane potential of colonic carcinoma cells is linked to the probability of tumor progression. Cancer Res. 65:9861–9867. 2005. View Article : Google Scholar : PubMed/NCBI

83 

Heerdt BG, Houston MA and Augenlicht LH: Growth properties of colonic tumor cells are a function of the intrinsic mitochondrial membrane potential. Cancer Res. 66:1591–1596. 2006. View Article : Google Scholar : PubMed/NCBI

84 

Ye XQ, Li Q, Wang GH, Sun FF, Huang GJ, Bian XW, Yu SC and Qian GS: Mitochondrial and energy metabolism-related properties as novel indicators of lung cancer stem cells. Int J Cancer. 129:820–831. 2011. View Article : Google Scholar : PubMed/NCBI

85 

Michelakis ED, Sutendra G, Dromparis P, Webster L, Haromy A, Niven E, Maguire C, Gammer TL, Mackey JR, Fulton D, et al: Metabolic modulation of glioblastoma with dichloroacetate. Sci Transl Med. 2:31ra342010. View Article : Google Scholar : PubMed/NCBI

86 

Pastò A, Bellio C, Pilotto G, Ciminale V, Silic-Benussi M, Guzzo G, Rasola A, Frasson C, Nardo G, Zulato E, et al: Cancer stem cells from epithelial ovarian cancer patients privilege oxidative phosphorylation, and resist glucose deprivation. Oncotarget. 5:4305–4319. 2014. View Article : Google Scholar : PubMed/NCBI

87 

Sun T, Ming L, Yan Y, Zhang Y and Xue H: Beclin 1 acetylation impairs the anticancer effect of aspirin in colorectal cancer cells. Oncotarget. 8:74781–74790. 2017.PubMed/NCBI

88 

Morselli E, Galluzzi L, Kepp O, Vicencio JM, Criollo A, Maiuri MC and Kroemer G: Anti- and pro-tumor functions of autophagy. Biochim Biophys Acta. 1793:1524–1532. 2009. View Article : Google Scholar : PubMed/NCBI

89 

Phi LT, Sari IN, Yang YG, Lee SH, Jun N, Kim KS, Lee YK and Kwon HY: Cancer stem cells (CSCs) in drug resistance and their therapeutic implications in cancer treatment. Stem Cells Int. 2018:54169232018. View Article : Google Scholar : PubMed/NCBI

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APA
Olejniczak-Kęder, A., Szaryńska, M., Wrońska, A., Siedlecka-Kroplewska, K., & Kmieć, Z. (2019). Effects of 5-FU and anti-EGFR antibody in combination with ASA on the spherical culture system of HCT116 and HT29 colorectal cancer cell lines. International Journal of Oncology, 55, 223-242. https://doi.org/10.3892/ijo.2019.4809
MLA
Olejniczak-Kęder, A., Szaryńska, M., Wrońska, A., Siedlecka-Kroplewska, K., Kmieć, Z."Effects of 5-FU and anti-EGFR antibody in combination with ASA on the spherical culture system of HCT116 and HT29 colorectal cancer cell lines". International Journal of Oncology 55.1 (2019): 223-242.
Chicago
Olejniczak-Kęder, A., Szaryńska, M., Wrońska, A., Siedlecka-Kroplewska, K., Kmieć, Z."Effects of 5-FU and anti-EGFR antibody in combination with ASA on the spherical culture system of HCT116 and HT29 colorectal cancer cell lines". International Journal of Oncology 55, no. 1 (2019): 223-242. https://doi.org/10.3892/ijo.2019.4809